Certain disease states require treatment using one or more different medicaments. Some drug compounds need to be delivered in a specific relationship with each other in order to deliver the optimum therapeutic dose. This invention is of particular benefit where combination therapy is desirable, but not possible in a single formulation for reasons such as, but not limited to, stability, compromised therapeutic performance and toxicology.
For example, in some cases it might be beneficial to treat a diabetic with a long acting insulin and with a glucagon-like peptide-1 (GLP-1), which is derived from the transcription product of the proglucagon gene. GLP-1 is found in the body and is secreted by the intestinal L cell as a gut hormone. GLP-1 possesses several physiological properties that make it (and its analogs) a subject of intensive investigation as a potential treatment of diabetes mellitus.
There are a number of potential problems when delivering two medicaments or active agents simultaneously. The two active agents may interact with each other during the long-term, shelf life storage of the formulation. Therefore, it is advantageous to store the active components separately and only combine them at the point of delivery, e.g. injection, needle-less injection, pumps, or inhalation. However, the process for combining the two agents needs to be simple and convenient for the user to perform reliably, repeatedly and safely.
A further problem is that the quantities and/or proportions of each active agent making up the combination therapy may need to be varied for each user or at different stages of their therapy. For example one or more actives may require a titration period to gradually introduce a patient up to a “maintenance” dose. A further example would be if one active requires a non-adjustable fixed dose while the other is varied in response to a patient's symptoms or physical condition. This problem means that pre-mixed formulations of multiple active agents may not be suitable as these pre-mixed formulations would have a fixed ratio of the active components, which could not be varied by the healthcare professional or user.
Additional problems arise where a multi-drug compound therapy is required, because many users cannot cope with having to use more than one drug delivery system or make the necessary accurate calculation of the required dose combination. This is especially true for users with dexterity or computational difficulties. In some circumstances it is also necessary to perform a priming procedure of the device and/or needle cannulae before dispensing the medicaments. Likewise, in some situations, it may be necessary to bypass one drug compound and to dispense only a single medicament from a separate reservoir.
Accordingly, there exists a strong need to provide devices and methods for the delivery of two or more medicaments in a single injection or delivery step that is simple for the user to perform. Our invention overcomes the above-mentioned problems by providing separate storage containers for two or more active drug agents that are then only combined and/or delivered to the patient during a single delivery procedure. Setting a dose of one medicament automatically fixes or determines the dose of the second medicament (i.e. non-user settable). Our invention also gives the opportunity for varying the quantity of one or both medicaments. For example, one fluid quantity can be varied by changing the properties of the injection device (e.g. dialing a user variable dose or changing the device's “fixed” dose). The second fluid quantity can be changed by manufacturing a variety of secondary drug containing packages with each variant containing a different volume and/or concentration of the second active agent. The user or healthcare professional would then select the most appropriate secondary package or series or combination of series of different packages for a particular treatment regime.
A number of medical and pharmaceutical drug delivery devices known in the art utilize the release of stored energy to drive some part of their mechanism during use. This energy may be stored in various forms including elastic (e.g. a spring), electrical, chemical, potential, pneumatic or hydraulic. In situations where this energy is captured/stored during the manufacturing or assembly process, rather than being provided by the user/patient as part of the use operation (such as winding a spring or pushing a lever), it is important that the energy is not accidentally released (triggered) until the desired moment, i.e., it is not prematurely released during transport or storage or similar such handling.
For some medical devices, accidental triggering prior to use may either compromise the operability of the device, or may even render it unusable. This may be of particularly importance for single-use devices. For devices containing medicament, and where accidental triggering has the potential to compromise the integrity of the primary pack of medicament, such events are likely to be particularly undesirable as they have the potential to result in a patient being exposed to a potentially non-sterile or even harmful, degraded form of the medicament.
Prior to use, the transit and storage of the medical device may present numerous scenarios in which the stored energy could be unintentionally discharged. Factors that may cause an accidental triggering event may include, but are not limited to; the application of static loads (stacking, crushing), dynamic loads (e.g. impact, vibration), pack and/or device inversion or temperature fluctuation.
Latches, locks and similar systems for preventing non-intentional actuation are known in the art (e.g. in the field of fire-arms, auto injectors, etc.). Generally, such features either need to be designed to be intuitive or, more ideally, the system designed in such a way that the shift in state from “locked out” to “triggerable” happens automatically as part of the standard, correct use procedure. Our invention provides such an automatic shift in state that prevents accidental triggering prior to use. Our invention is applicable to any device where energy may be stored in the device prior to delivery to the user, particularly single-use or medicated devices where accidental triggering may render the device unusable. Examples of such devices are auto-injectors, safety needles, safety syringes, needle-free/jet injectors and pressurized medicament cartridges (such as those used in pMDIs).
These and other advantages will become evident from the following more detailed description of the invention.